Whole-genome association study of antibody response to Epstein-Barr virus in an African population: a pilot

Author:

Sallah, N [ORCID]

Carstensen, T

Wakeham, K

Beyer, Rachel

Labo, Nazzarena

Pollard, M O

Gurdasani, D

Ekoru, K

Pomilla, C

Young, E H

Fatumo, S

Asiki, G

Kamali, A

Sandhu, M

Kellam, P

Whitby, Denise

Barroso, I

Newton, R
Author Address

Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK., Department of Virus Genomics, Wellcome Trust Sanger Institute, Hinxton, UK., Department of Medicine, University of Cambridge, Cambridge, UK., MRC/Uganda Virus Research Institute, Uganda Research Unit on AIDS, Entebbe, Uganda., Institute of Cancer Sciences, University of Glasgow, Glasgow, UK., Protein Expression Lab, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Viral Oncology Section, Aids and Cancer Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., H3Africa Bioinformatics Network (H3ABioNet) Node, National Biotechnology Development Agency (NABDA), Federal Ministry of Science and Technology (FMST), Abuja, Nigeria.,

Abstract:

Epstein Barr virus (EBV) infects 95% of the global population and is associated with up to 2% of cancers globally. Immunoglobulin G (IgG) antibody levels to EBV have been shown to be heritable and associated with developing malignancies. We, therefore, performed a pilot genome-wide association analysis of anti-EBV IgG traits in an African population, using a combined approach including array genotyping, whole-genome sequencing and imputation to a panel with African sequence data. In 1562 Ugandans, we identify a variant in human leukocyte antigen (HLA)-DQA1, rs9272371 (p = 2.6 215; 10-17) associated with anti-EBV nuclear antigen-1 responses. Trans-ancestry meta-analysis and fine-mapping with European-ancestry individuals suggest the presence of distinct HLA class II variants driving associations in Uganda. In addition, we identify four putative, novel, very rare African-specific loci with preliminary evidence for association with anti-viral capsid antigen IgG responses which will require replication for validation. These findings reinforce the need for the expansion of such studies in African populations with relevant datasets to capture genetic diversity.

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Author Address